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A Genomic Epidemiology Study of Multidrug-Resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii in Two Intensive Care Units in Hanoi, Vietnam

23 Pages Posted: 28 Sep 2021

See all articles by Leah W. Roberts

Leah W. Roberts

European Bioinformatics Institute (EMBL-EBI) - Wellcome Genome Campus

Le Thi Hoi

National Hospital for Tropical Diseases

Fahad A. Khokhar

University of Cambridge - Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID)

Nguyen Thi Hoa

National Hospital for Tropical Diseases

Tran Van Giang

National Hospital for Tropical Diseases

Cuong Bui

Bach Mai Hospital

Tran Hai Ninh

National Hospital for Tropical Diseases

Dao Xuan Co

Bach Mai Hospital

Nguyen Gia Binh

Bach Mai Hospital

Hoang Bao Long

Hospital of Tropical Diseases - Oxford University Clinical Research Unit

Huong Dang

Hanoi Medical University

James E. Bryan

University of Cambridge

Archie Herrick

University of Cambridge

Theresa Feltwell

University of Cambridge

Behzad Nadjm

Hospital of Tropical Diseases - Oxford University Clinical Research Unit

H. Rogier van Doorn

Hospital of Tropical Diseases - Oxford University Clinical Research Unit

Julian Parkhill

University of Cambridge - Department of Veterinary Medicine

Nguyen Vu Trung

National Hospital for Tropical Diseases

Nguyen Van Kinh

National Hospital for Tropical Diseases

Zamin Iqbal

European Bioinformatics Institute (EMBL-EBI)

Mili Estée Török

University of Cambridge - Department of Medicine; NHS Foundation Trust - Cambridge University Hospitals

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Abstract

Background: Vietnam has high rates of antimicrobial resistance (AMR) but limited capacity for genomic surveillance. This study used whole genome sequencing (WGS) to examine the prevalence and transmission of three key AMR pathogens in two intensive care units in Hanoi, Vietnam.

Methods: A prospective surveillance study of all adults admitted to intensive care units (ICUs) at the National Hospital for Tropical Diseases (NHTD) and Bach Mai Hospital (BMH) was conducted between June 2017 and January 2018. Clinical and environmental samples were cultured on selective media, characterised using MALDI TOF MS, and illumina sequenced. Phylogenies based on the de novo assemblies (SPAdes) were constructed using Mafft (PARsnp), Gubbins and RAxML. Resistance genes were detected using Abricate against the NCBI database.

Findings: 3,153 Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A. baumannii (global clone [GC]2, sequence types [ST]2, ST571) and K. pneumoniae (ST15, ST16, ST656, ST11, ST147) isolates. Colonisation was most common with E. coli (88.9%) followed by K. pneumoniae (62.4%). Of the E. coli, 91% carried a blaCTX-M variant, while 81% of K. pneumoniae isolates carried blaNDM (54%) and/or blaKPC (45%). Transmission analysis using single nucleotide polymorphisms (SNPs) identified 167 clusters involving 251 (68%) patients, in some cases involving patients from both ICUs. There were no significant differences between the lineages or AMR genes recovered between the two ICUs.

Interpretation: This study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission prior to ICU admission in other healthcare settings or in the community.

Funding Information: This study was funded by the UK Medical Research Council Newton Fund (grant MR/N029399/1); the Ministry of Science and Technology, Vietnam (grant HNQT/SPÐP/04.16) and the Wellcome Trust (grant 206194). LWR is supported by EMBL-EBI biomedical postdoctoral research fellowship. MET was supported by a Clinician Scientist Fellowship (funded by the Academy of Medical Sciences and the Health Foundation) and the National Institutes of Health Research Cambridge Biomedical Research Centre.

Declaration of Interests: All authors declare no conflicts of interest.

Ethics Approval Statement: The study protocol was approved by the Scientific and Ethical Committees of the National Hospital for Tropical Diseases and Bach Mai Hospital and by the University of Cambridge Human Biology and Research Ethics Committee (reference: HBREC 2017.09). Written informed consent was obtained from the patient or from their relative prior to enrolment in the study.

Keywords: antimicrobial resistance, multidrug-resistant, whole genome sequencing, E. coli, K. pneumoniae, A. baumannii, transmission, intensive care, Vietnam

Suggested Citation

Roberts, Leah W. and Hoi, Le Thi and Khokhar, Fahad A. and Hoa, Nguyen Thi and Van Giang, Tran and Bui, Cuong and Ninh, Tran Hai and Co, Dao Xuan and Binh, Nguyen Gia and Long, Hoang Bao and Dang, Huong and Bryan, James E. and Herrick, Archie and Feltwell, Theresa and Nadjm, Behzad and van Doorn, H. Rogier and Parkhill, Julian and Trung, Nguyen Vu and Van Kinh, Nguyen and Iqbal, Zamin and Török, Mili Estée, A Genomic Epidemiology Study of Multidrug-Resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii in Two Intensive Care Units in Hanoi, Vietnam. Available at SSRN: https://ssrn.com/abstract=3932254 or http://dx.doi.org/10.2139/ssrn.3932254

Leah W. Roberts

European Bioinformatics Institute (EMBL-EBI) - Wellcome Genome Campus ( email )

Cambridge
United Kingdom

Le Thi Hoi

National Hospital for Tropical Diseases ( email )

Hanoi
Vietnam

Fahad A. Khokhar

University of Cambridge - Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID) ( email )

Cambridge
United Kingdom

Nguyen Thi Hoa

National Hospital for Tropical Diseases ( email )

Hanoi
Vietnam

Tran Van Giang

National Hospital for Tropical Diseases ( email )

Hanoi
Vietnam

Cuong Bui

Bach Mai Hospital

Hanoi
Vietnam

Tran Hai Ninh

National Hospital for Tropical Diseases ( email )

Hanoi
Vietnam

Dao Xuan Co

Bach Mai Hospital ( email )

Hanoi
Vietnam

Nguyen Gia Binh

Bach Mai Hospital ( email )

Hanoi
Vietnam

Hoang Bao Long

Hospital of Tropical Diseases - Oxford University Clinical Research Unit ( email )

Hanoi
Vietnam

Huong Dang

Hanoi Medical University ( email )

James E. Bryan

University of Cambridge ( email )

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Archie Herrick

University of Cambridge ( email )

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Theresa Feltwell

University of Cambridge ( email )

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Behzad Nadjm

Hospital of Tropical Diseases - Oxford University Clinical Research Unit ( email )

Vietnam

H. Rogier Van Doorn

Hospital of Tropical Diseases - Oxford University Clinical Research Unit ( email )

Julian Parkhill

University of Cambridge - Department of Veterinary Medicine

Cambridge
United Kingdom

Nguyen Vu Trung

National Hospital for Tropical Diseases ( email )

Hanoi
Vietnam

Nguyen Van Kinh

National Hospital for Tropical Diseases ( email )

Hanoi
Vietnam

Zamin Iqbal

European Bioinformatics Institute (EMBL-EBI) ( email )

Wellcome Genome Campus, Hinxton
Cambridge
United Kingdom

Mili Estée Török (Contact Author)

University of Cambridge - Department of Medicine ( email )

United Kingdom

NHS Foundation Trust - Cambridge University Hospitals ( email )

Hills Road
Cambridge, CB2 0QQ
United Kingdom